Inherited predisposition to pneumothorax: Estimating the frequency of Birt-Hogg-Dubé syndrome from genomics and population cohorts
Publication: Thorax
Bryndis Yngvadottir, Lucy Richman, Avgi Andreou, Jessica Woodley, Anita Luharia, Derek Lim, Eamonn R Maher, Stefan J Marciniak
10 April 2025
A condition called Birt-Hogg-Dubé syndrome (BHDS) is the most common single genetic cause of pneumothorax (a collection of air in the pleural space between the lung and the chest wall). Families that are affected have disease causing changes in the FLCN gene. Marciniak et al used large genomic registries (UK Biobank, 100K Genomes Project and East London Genes & Health) to look at the health data of >550,000 individuals and discovered that the frequency of clinically proven loss-of-function FLCN variants is 1 in 2710 to 4190 people. The lifetime risk of pneumothorax in FLCN mutation carriers in the UKB cohort was (28.4%) and BHDS cohort (37.3%) up to the age of 65 years. The lifetime risk of renal cancer was much lower in the UKB group (1%) than the BHDS patients (32.1%). The findings show the importance of clinical context in managing people with FLCN mutations.
